1. Field of the Invention
The present invention relates to an improved solution to protect the heart, kidney and other organs from being damaged by blood circulation stoppage during operations and transplant as well as to a process for the preparation of such a solution.
2. Description of the Prior Art
New surgical procedures for reconstructing serious congenital deformations of the heart, improvements in cardiac valve protheses and advances in the surgery of coronary vessels have opened up the possibility of completely restoring the health of the most seriously ill. While the heart-lung machine technique only minimally hinders the results of complicated heart operations, the ischemia tolerance, i.e., the tolerance of the organ to a complete interruption of its blood and oxygen supply by disconnecting it from the total circulation, is still an important limiting factor.
After completely interrupting the blood and oxygen supply, the energy balance and the functional capacity of the heart are disturbed rapidly. For this reason, the method of separately supplying the coronary vessels more or less continuously with blood by means of special pumps and cannulae is practiced by some heart surgeons. This coronary perfusion technique is however also associated with serious disadvantages. Namely, the main branches of the coronary vessels cannot always be cannulated completely, the coronary catheters and the organ, supplied with blood, hinder the field of the operation, and the beating heart makes the use of microsurgical methods with the surgical microscope impossible.
For this reason, the technique of artificially stopping the heart with total interruption of the blood supply was developed. The ischemic stopped heart survives for 20 to 40 minutes, depending on previous damage and on the temperature. The exhaustion of energy reserves, which arises in such a procedure, frequently makes a prolonged period of recovery necessary, with use of the heart-lung machine to relieve the stress on the heart, and necessitates an intensive supervision of the more endangered patients in the first postoperative days. In addition, because of the different and complicated surgical interventions, the surgeon is under a considerable time pressure because he must avoid exceeding the very limited ischemia tolerance time under all circumstances.
The limited duration of the operation in the purely ischemic cardiac standstill was the inducement for numerous attempts to improve the protection of the myocardium, for example, through acetylcholine, through magnesium salts, through novocaine, and through the sodium-deficient, calcium-free, novocaine-containing cardioplegic solution, described by H. J. Bretschneider in 1964 (H. J. Bretschneider: Survival and Resuscitation Times of the Heart in the Case of Normothermy and Hypothermy; Verh. Dtsch. Ges. Kreislaufforschg., 30 (1964), 11; H. J. Bretschneider, G. Hubner, D. Knoll, B. Lohr, H. Nordbeck and P. G. Spieckermann: Myocardial Resistance and Tolerance to Ischemia: Physiological and Biochemical Basis; J. of Cardiovasc. Surg., 16 (1975) 241). This cardioplegic solution guarantees an ischemia tolerance time which is approximately twice that of the purely ischemic cardiac standstill. Nevertheless, because of the great advances in surgical techniques, it has become urgent that the duration of ischemia, which is well tolerated by the heart, be lengthened even further and extended to 100 to 120 minutes at 30.degree. C. At the same time, the recovery time necessary must remain as short as possible; only about 10 minutes, in order to keep the total length of time, during which the heart-lung machine is used, as short as possible.
In European patent application No. 12272, a protective solution for the heart, kidneys and other organs is described which is characterized by a buffer system based on histidine, histidine hydrochloride, and tryptophane and which additionally contains sodium, potassium and magnesium ions as well as a polyol or a sugar. With such a protective solution, an ischemia tolerance time having an improvement factor of 4-8 relative to the unaffected heart can be attained.